Active immunization is the administration of an antigen to an animal to bring about an immune response in the animal. A vaccine against a microorganism is an antigenic preparation which when inoculated into a non-immune individual will confer active immunity to the microorganism but will not cause disease. Specificity and memory, the two key elements of the adaptive immune system, are exploited in vaccination, since the adaptive immune system mounts a much stronger response on second encounter with an antigen. This secondary immune response is both faster to appear and more effective than the primary response. The principle of vaccine development is to alter a microorganism or its toxins (natural antigens) in such a way that they become innocuous without losing antigenicity. Alternatively, antigenic polypeptides of the organism in question can be produced by recombinant methods or by synthetic chemistry to produce an effective vaccine.
One problem that frequently is encountered in the course of active immunization is that the antigens used in the vaccine are not sufficiently immunogenic to raise antibody titer to sufficient levels to provide protection against subsequent challenge, or to maintain the potential for mounting these levels over extended time periods. Another problem is that the vaccine may be deficient in inducing cell-mediated immunity which is a primary immune defense against bacterial and viral infection. Still another problem is that an individual patient might be immunocompromised due to illness or age.
To obtain a stronger humoral and/or cellular response, it is common to administer a vaccine in a formulation containing an adjuvant. An adjuvant is a substance that enhances, nonspecifically, the immune response to an antigen, or which causes an individual to respond to an antigen who would otherwise without the adjuvant not respond to the antigen. An adjuvant is usually administered with an antigen, but may also be given before or after antigen administration.
However, in spite of the many advances in vaccines and vaccine preparation, very often vaccines do not give the immunogenic response desired especially in the immunocompromised and the aged. An example is the pneumococcal vaccine PNU-IMUNE 23. Pneumococcal pneumonia is currently the most common cause of bacterial pneumonia in the United States, and the rate of this disease is especially high in the elderly, young children, patients with predisposing conditions such as asplenia, chronic heart, lung and kidney disease, diabetics and patients suffering from genetic or acquired immunosuppression (Breiman et. al. Arch. Intern. Med. 150: 1401-1404 (1990)). These groups are at greater risk of pneumococcal spread to the blood and the central nervous system which is the most common cause of bacterial meningitis. This vaccine has a aggregate efficacy of approximately 75% in immunocompetent adults, but the coverage in the high-risk groups listed above has been debated, and is certainly much lower (Butler et. al. J. Am. Med. Assoc. 270: 1826 (1993). Thus, there is a need for additional aids or adjuvants which can be administered in conjunction with a vaccine to bring about an immunizing effect to the aged and immunocompromised.